Studies of the escape of solute from plasma usually consider the capillary wall to be the primary barrier to movement. However, recent physiological and physicochemical evidence concerning the interstitium and its macromolecules have strongly suggested that the interstitial matrix might contribute significantly to the transport resistances for solute and water. The research will measure the diffusion rates of various solutes from plasma under various hydration states, including osmotic shift of water from cells, using an isogravimetric hindlimb preparation. The data will be interpreted using mathematical models of the transport system. The effects of certain proteolytic enzymes, known to disrupt the interstitial matrix, on transport rates will be investigated.